Antitumor activity of methyl (5-fluoro-1H-2-oxo-4-pyrimidinyl beta-D-glucopyranosid)uronate against various experimental tumors.
The antitumor activity of a glucuronide of 5-fluorouracil, methyl (5-fluoro-1H-2-oxo-4-pyrimidinyl beta-D-glucopyranosid) uronate (FU-O-G), which is a 5-fluorouracil (5-FU) derivative with remarkably low toxicity, was studied. The antitumor activity of this compound was superior to those of 5-FU and 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, Ftorafur) in the treatment of transplantable tumors, not only 5-FU-sensitive tumors such as adenocarcinoma 755, lymphosarcoma LS-1, and plasmacytoma X5563, but also 5-FU-resistant tumors such as Lewis lung carcinoma and Walker carcinosarcoma 256. Furthermore, in the treatment of Lewis lung carcinoma, which responds poorly to 5-FU and Ftorafur, daily administration of FU-O-G at a dose of 400 mg/kg for 30 days produced a 92% increase in life span without marked loss of body weight, though short-term administration (such as 5 days) was barely effective. Thus, it appears that FU-O-G is an antitumor agent suitable for long-term administration. These findings correspond with the results of an enzymological study which showed selective activation of FU-O-G by beta-glucosidase in tumor cells and indicated that the compound is a marked form of 5-FU.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000031:analogs & derivatives; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011741:Pyrimidine Nucleosides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D005641:Tegafur / Q000494:pharmacology; D013997:Time Factors
D000970:Antineoplastic Agents; D011741:Pyrimidine Nucleosides; D005641:Tegafur; C018604:methyl 1-(5-fluoro-1H-2-oxopyrimidin-4-yl)-beta-D- glucopyranuronate; D005472:Fluorouracil